Biomedical subjects

Bradford Towne

Publications and source records attributed to Bradford Towne.

15 recordsLinked to original sources

PubMed2006

Quantitative genetics of cortical bone mass in healthy 10-year-old children from the Fels Longitudinal Study.

The genetic influences on bone mass likely change throughout the life span, but most genetic studies of bone mass regulation have focused on adults. There is, however, a growing awareness of the importance of genes influencing the acquisition of bone mass during childhood on lifelong bone health. The present investigation examines genetic influences on childhood bone mass by estimating the residual heritabilities of different measures of second metacarpal bone mass in a sample of 600 10-year-old participants from 144 families in the Fels Longitudinal Study. Bivariate quantitative genetic analyses were conducted to estimate genetic correlations between cortical bone mass measures, and measures of bone growth and development. Using a maximum likelihood-based variance components method for pedigree data, we found a residual heritability estimate of 0.71 for second metacarpal cortical index. Residual heritability estimates for individual measures of cortical bone (e.g., lateral cortical thickness, medial cortical thickness) ranged from 0.47 to 0.58, at this pre-pubertal childhood age. Low genetic correlations were found between cortical bone measures and both bone length and skeletal age. However, after Bonferonni adjustment for multiple testing, rho(G) was not significantly different from 0 for any of these pairs of traits. Results of this investigation provide evidence of significant genetic control over bone mass largely independent of maturation while bones are actively growing and before rapid accrual of bone that typically occurs during puberty.

Bone Density↗

PubMed2006

A quantitative trait locus (QTL) on chromosome 6q influences birth weight in two independent family studies.

Low birth weight is an important cause of infant mortality and morbidity worldwide. Birth weight has been shown to be inversely correlated with adult complex diseases such as obesity, type-2 diabetes and cardiovascular disease. However, little is known about the genetic factors influencing variation in birth weight and its association with diseases that occur in later life. We, therefore, have performed a genome-wide search to identify genes that influence birth weight in Mexican-Americans using the data from the San Antonio Family Birth Weight Study participants (n=840). Heritability of birth weight was estimated as 72.0+/-8.4% (P<0.0001) after adjusting for the effects of sex and term. Multipoint linkage analysis yielded the strongest evidence for linkage of birth weight (LOD=3.7) between the markers D6S1053 and D6S1031 on chromosome 6q. This finding has been replicated (LOD=2.3) in an independent European-American population. Together, these findings provide substantial evidence (LOD(adj)=4.3) for a major locus influencing variation in birth weight. This region harbors positional candidate genes such as chorionic gonadotropin, alpha chain; collagen, type XIX, alpha-1; and protein-tyrosine phosphatase, type 4A, 1 that may play a role in fetal growth and development. In addition, potential evidence for linkage (LOD>or=1.2) was found on chromosomes 1q, 2q, 3q, 4q, 9p, 19p and 19q with LODs ranging from 1.3 to 2.7. Thus, we have found strong evidence for a major gene on chromosome 6q that influences variation in birth weight in both Mexican- and European-Americans.

Birth Weight↗

PubMed2006

Radiographic joint space of the knee in healthy young adults.

The primary objective of this study was to characterize normal variation in radiographic joint space of the knee in a large sample of healthy young adults and to identify factors that contribute to this variation. We measured radiographic knee joint space in 279 skeletally mature subjects, age between 16 and 22 years, who participated in the Fels Longitudinal Study. Minimum joint space was measured in the medial and lateral knee compartments. Independent sample t tests and correlation analyses were performed to examine sex differences and associations between joint space, joint size, and body size [weight, stature, body mass index (BMI)]. Results show that young men have thicker articular cartilage than young women in both the medial and lateral compartments of the knee. Significant positive correlations were found between joint space and body size measures in the total sample. When the sexes were considered independently, however, correlations between joint space and body size were significant in men only. Regression analyses of the combined-sex sample identified sex, BMI, and joint width as significant explanatory factors of medial joint space, together accounting for 26% of the observed variance. In contrast, sex was the sole significant explanatory factor of lateral joint space, explaining 19% of the observed variance. Results of this study show that during early adulthood, when articular cartilage is healthy and at its peak thickness, men have thicker knee cartilage than women. At this young age body size accounts for a modest proportion of the variation observed in knee cartilage thickness.

Adolescent↗

PubMed2006

Do changes in body mass index percentile reflect changes in body composition in children? Data from the Fels Longitudinal Study.

OBJECTIVE: Our aim was to examine the degree to which changes in BMI percentile reflect changes in body fat and lean body mass during childhood and how age and gender affect these relationships. METHODS: This analysis used serial data on 494 white boys and girls who were aged 8 to 18 years and participating in the Fels Longitudinal Study (total 2319 observations). Total body fat (TBF), total body fat-free mass (FFM), and percentage of body fat (%BF) were determined by hydrodensitometry, and then BMI was partitioned into its fat and fat-free components: fat mass index (FMI) and FFM index (FFMI). We calculated predicted changes (Delta) in FMI, FFMI, and %BF for each 10-unit increase in BMI percentile using mixed-effects models. RESULTS: FFMI had a linear relationship with BMI percentile, whereas FMI and %BF tended to increase dramatically only at higher BMI percentiles. Gender and age had significant effects on the relationship between BMI percentile and FFMI, FMI, and %BF. Predicted Delta%BF for boys 13 to 18 years of age was negative, suggesting loss of relative fatness for each 10-unit increase in BMI percentile. CONCLUSIONS: In this longitudinal study of white children, FFMI consistently increased with BMI percentile, whereas FMI and %BF had more complicated relationships with BMI percentile depending on gender, age, and whether BMI percentile was high or low. Our results suggest that BMI percentile changes may not accurately reflect changes in adiposity in children over time, particularly among male adolescents and children of lower BMI.

Adolescent↗

PubMed2005

The development of sex differences in digital formula from infancy in the Fels Longitudinal Study.

Relative finger lengths, especially the second-to-fourth finger length ratio, have been proposed as useful markers for prenatal testosterone action. This claim partly depends on an association of relative finger lengths in adults with related sex differences in children and infants. This paper reports the results of a study using serial radiographs to test for both sex differences in the fingers of infants and children and for a relationship between sex differences in the children and infant finger and adult finger length ratios. This is the first study using long-term serial data to evaluate the validity of finger length ratios as markers. We found not only that sex differences in finger length ratios arise prior to puberty, but that sex differences in the fingers of children are highly correlated with adult finger length ratios. Our results strongly encourage the further use of finger length ratios as markers of perinatal testosterone action.

Adolescent↗

PubMed2005

Quantitative genetic analysis of cellular adhesion molecules: the Fels Longitudinal Study.

Circulating concentrations of inflammatory markers predict cardiovascular disease (CVD) risk and are closely associated with obesity. However, little is known concerning genetic influences on serum levels of inflammatory markers. In this study, we estimated the heritability (h2) of soluble cellular adhesion molecule (sCAM) concentrations and examined the correlational architecture between different sCAMs. The study population included 234 men and 270 women aged 18-76 years, belonging to 121 families participating in the Fels Longitudinal Study. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sESEL-1) and P-selectin (sPSEL-1) were assayed using commercially available kits. A variance components-based maximum likelihood method was used to estimate the h2 of the different serum inflammatory markers while simultaneously adjusting for the effects of known CVD risk factors, such as age and smoking. Additionally, we used bivariate extensions of these methods to estimate genetic and random environmental correlations among sCAMs. Levels of sCAMs were significantly heritable: h2=0.24+/-0.10 for sICAM-1, h2=0.22+/-0.10 for sVCAM-1, h2=0.50+/-0.11 for sESEL-1, and h2=0.46+/-0.10 for sPSEL-1. In addition, a significant genetic correlation (rho(G)=0.63) was found between sICAM-1 and sVCAM-1 indicating some degree of shared genetic control. In the Fels Longitudinal Study, the levels of four sCAMs are significantly influenced by genetic effects, and sICAM-1 shares a common genetic background with sVCAM-1.

Adolescent↗

PubMed2005

Heritability of age at menarche in girls from the Fels Longitudinal Study.

Menarche is the hallmark maturational event of female childhood. Many studies indicated a significant genetic contribution to the timing of the onset of menstruation, but most of these studies were limited by the use of retrospective data and by the use of data from only certain types of relatives (i.e., mothers and daughters, sisters, or twin sisters). The primary goal of this study was to use a modern maximum likelihood quantitative genetic method to estimate the heritability (h(2)) of age at menarche, using familial data collected over the course of the 74-year-old Fels Longitudinal Study. The secondary goal was to review earlier studies of the heritability of age at menarche. The study of the heritability of age at menarche presented here is unique for two reasons. First, because of the Fels Longitudinal Study's serial design, age-at-menarche data were collected prospectively from most participants. Second, because the Fels Longitudinal Study is a family study that has been conducted for decades, age-at-menarche data are available from many types of female relatives spanning multiple households and generations. The best-fitting and most parsimonious quantitative genetic model included provision for a secular decrease in age at menarche, and estimated the h(2) of age at menarche to be 0.49+/- 0.13 (95% confidence interval of h(2),=0.24-0.73). The results of this study are in general agreement with the findings of most previous studies of genetic influences on age at menarche, and suggest that it is reasonable to consider it well-established that approximately half the phenotypic variation among girls from developed nations in the timing of menarche is due to genetic factors.

Adolescent↗

PubMed2005

Quantitative genetic analysis of blood pressure response during the cold pressor test.

BACKGROUND: The genetic association between blood pressure (BP) at rest and during the cold pressor test (CPT) is not well characterized. The purpose of this study was to examine the genetic architecture of BP during the CPT, and to determine whether BP at rest and during the CPT share common genetic influences. METHODS: In 419 individuals distributed across four large families, variance components methods were used to estimate heritabilities of resting BP and CPT BP, along with genetic correlations among BP traits. The CPT consisted of immersion of the left foot in 4 degrees C water while the participant was supine. Blood pressure reactivity (DeltaBP) was defined as BP at 15 to 30 sec and 45 to 60 sec of foot immersion minus resting BP. RESULTS: Significant (P < .05) heritabilities were found for supine BP (h(2)(SBP) = 0.35), CPT BP (h(2)(SBP) = 0.27 and 0.33, h(2)(DBP) = 0.18 and 0.30), and DeltaSBP (h(2)(SBP) = 0.12 and 0.37) but not for DeltaDBP. Bivariate analyses detected significant (P < .05) genetic correlations between resting SBP and CPT SBP that were different from 0 and 1. Genetic correlations between resting DBP and CPT DBP were not significantly different from 1. Genetic correlations between resting SBP and DeltaSBP were not significant. CONCLUSIONS: Measures of BP at rest and during cold immersion are significantly influenced by additive genetic effects. These genetic influences are only partially shared between SBP at rest and SBP during cold immersion, suggesting that a somewhat different set of genes may influence SBP during cold immersion. Unique sets of genes also appear to influence DeltaSBP independent of those influencing resting SBP.

Adolescent↗

PubMed2005

The case for strategic international alliances to harness nutritional genomics for public and personal health.

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.

Animals↗

PubMed2004

Heritability of calcaneal quantitative ultrasound measures in healthy adults from the Fels Longitudinal Study.

Quantitative ultrasound (QUS) measurements of bone have been reported to predict osteoporotic fracture risk in postmenopausal women and older men. Although many studies have examined the heritability of bone mineral density (BMD), few studies have estimated the heritability of calcaneal QUS phenotypes. In the present study, we examined the genetic regulation of calcaneal QUS parameters in individuals from nuclear and extended families. The study population includes 260 men and 295 women aged 18-91 years (mean+/-SD: 46+/-16 years) who belong to 111 pedigrees in the Fels Longitudinal Study. Three measures of calcaneal structure were collected from both the right and left heel using the Sahara bone sonometer. These measures included broadband ultrasound attenuation (BUA), speed of sound (SOS), and the quantitative ultrasound index (QUI). We used a variance components based maximum likelihood method to estimate the heritability of QUS parameters while simultaneously adjusting for covariate effects. Additionally, we used bivariate extensions of these methods to calculate additive genetic and random environmental correlations among QUS measures. All phenotypes demonstrated statistically significant heritabilities (P<0.0000001). Heritabilities in the right heel (h2+/-SE) were h2=0.59+/-0.10 for BUA, h2=0.73+/-0.09 for SOS, and h2=0.72+/-0.09 for QUI. Similarly, heritabilities for the left heel were h2=0.52+/-0.10, h2=0.75+/-0.10, and h2=0.70+/0.10, respectively. There was evidence for significant genetic and environmental correlations among these six QUS measures. Combinations of QUS measures in the right and left heel demonstrated genetic correlations of 0.94-0.99 and all were significantly different from one indicating at least a partially unique genetic architecture for each of these measures. This study demonstrates that QUS measures of the calcaneus among healthy men and women are heritable, and there are large shared additive genetic effects among all of the traits examined.

Adolescent↗

PubMed2004

Fifty-year trends in serial body mass index during adolescence in girls: the Fels Longitudinal Study.

BACKGROUND: A decline in the age at menarche was recently reported for US girls. Although it is possible that this recent drop stems from the concurrent increase in childhood obesity, few longitudinal studies of growth and development have been undertaken to specifically address the temporal relation between growth, adiposity, and the age at menarche. OBJECTIVE: The objective was to simultaneously examine the effects of birth cohort (secular trend) and rate of maturation (age at menarche) on the timing and pattern of increases in body mass index (BMI) during adolescence in girls. DESIGN: We applied mixed-effects polynomial models to serial BMI data, spanning from 6 y before menarche to 6 y after menarche, obtained from 211 girls enrolled in the Fels Longitudinal Study. We examined the effects of birth cohort (defined as girls born 1929-1946, 1947-1964, and 1965-1983) and age at menarche (defined as < or =11.9 y, 12.0-13.1 y, and > or =13.2 y) on the magnitude and velocity of BMI during adolescence. RESULTS: BMI and BMI velocity in girls born after 1965 were significantly greater than those of girls of earlier birth cohorts, despite stability in the mean age at menarche. Although girls with early menarche tended to have significantly higher BMIs than did girls with average or later menarche, these differences did not emerge until after menarche. CONCLUSION: These data suggest that increases in relative weight are a consequence, rather than a determinant, of the age at menarche and that secular changes in BMI and in the mean age at menarche could be independent phenomena.

Adolescent↗

PubMed2004

Telomeres and telomerase in the fetal origins of cardiovascular disease: a review.

Telomeres are noncoding functional DNA repeat sequences at the ends of chromosomes that decrease in length by a predictable amount at each cell division. When the telomeres become critically short, the cell is no longer able to replicate and enters cellular senescence. Recent work has shown that within individuals, telomere length tracks with cardiovascular health and aging and is also affected by growth variation, both prenatally and postnatally. Therefore telomere length can be a marker of both growth history (cell division) and tissue function (senescence). Relationships between early growth and later health have emerged as a research focus in the epidemiology of chronic diseases of aging, such as heart disease and diabetes. The "fetal origins" literature has demonstrated that hormonal and nutritional aspects of the intrauterine environment not only affect fetal growth but also can permanently alter the metabolic program of the individual. Smaller infants tend to have a higher risk of developing cardiovascular disease. Much less attention has been paid to possible genetic links between the processes of early growth and later disease. Our aim in this review is to summarize evidence for one such genetic mechanism, telomere attrition, that may underlie the fetal origins of cardiovascular disease and to discuss this mechanism in light of the evolution of senescence.

Aging↗

PubMed2004

The belated autopsy and identification of an eighteenth century naval hero--the saga of John Paul Jones.

John Paul Jones, the "Father of the American Navy," is known for the battletime assertion that he had "not yet begun to fight." His central role in a triumph of scientific forensic identification more than a century after his death is less known. John Paul Jones died in 1792 and was buried in Paris, France. The location of his grave was lost over time and a search for his corpse began in 1899. Remains matching his physical characteristics and circumstance of burial were discovered in 1905 and returned to the United States for a hero's burial. Some questioned the identification at the time and the major source of identifying information has since been shown to contain false information. The published forensic literature fails to address existing critiques of the identification. We provide a substantive analysis and conclude that the available evidence supports the identification of the unknown remains as those of John Paul Jones.

Autopsy↗

PubMed2003

Puberty and body composition.

Body composition during puberty is a marker of metabolic changes that occur during this period of growth and maturation, and, thus, holds key information regarding current and future health. During puberty, the main components of body composition (total body fat, lean body mass, bone mineral content) all increase, but considerable sexual dimorphism exists. Methods for measuring body composition (e.g. densitometry and dual-energy X-ray absorptiometry) and degree of maturity will be discussed in this review. Components of body composition show age-to-age correlations (i.e. 'tracking'), especially from adolescence onwards. Furthermore, adipose tissue is endocrinologically active and is centrally involved in the interaction between adipocytokines, insulin and sex-steroid hormones, and thus influences cardiovascular and metabolic disease processes. In conclusion, pubertal body composition is important, not only for the assessment of contemporaneous nutritional status, but also for being linked directly to the possible onset of chronic disease later in life and is, therefore, useful for disease risk assessment and intervention early in life.

Adolescent↗

PubMedDate not supplied

Recent decline in age at menarche: the Fels Longitudinal Study.

A number of recent reports suggest that the average age at menarche of US girls has declined over the past 20 years. Because the putative declines in the age at menarche are concurrent with increases in childhood body mass index (BMI), it has been suggested that these two trends may be causally linked. We examined differences in mean age of menarche in Fels Longitudinal Study girls who were born in six 10-year birth cohorts (1930s, 1940s, 1950s, 1960s, 1970s, and 1980s) and simultaneous cohort changes in mean BMI measured cross-sectionally at selected ages from 3-35 years (n = 371). Girls born in the 1980s had a mean age at menarche of 12.34 years, which was approximately 3-6 months earlier than that of girls born previously (P < 0.001). While the mean BMI values at ages 25 and 35 generally increased from the 1930s to the 1970s, the mean BMI during childhood and adolescence remained constant across the six birth cohorts. In summary, we found no evidence that the recent decline in the age at menarche in the Fels Longitudinal Study girls was reflected in concurrent increases in BMI at any point in childhood or adolescence. Conversely, girls born in the 1960s and 1970s have subsequently become heavier in young and mid-adulthood than were girls from earlier birth cohorts, without any concurrent change in the mean age at menarche over that time period. These two findings suggest that population-level shifts in BMI and the timing of menarche are largely independent, although sometimes coincident, processes.

Adolescent↗